Primary hepatoma often occurs in the setting of established cirrhosis of any cause. In fact, abrupt deterioration of a patient with known cirrhosis is a signal to consider the possibility of HCC. Other pathogenic antecedents of HCC include hepatitis C virus, chronic hepatitis B virus infection (HBV) with or without cirrhosis, exposure to aflatoxins in food (implicated in parts of Africa and Asia), and exposure in the distant past to thorium dioxide, a radiologic contrast material, nonalcoholic steatohepatitis (NASH) associated with obesity and diabetes mellitus. Uncommon consequences of HCC include fever of unknown origin, portal vein thrombosis, hypoglycemia, polycythemia, hypercalcemia, porphyria, and dysglobulinemia.

The incidence of HCC has doubled in the United States for the past 20 years and continues to increase due to HCV- and HBV-related complications and NASH-related cirrhosis.

The mean age at the time of diagnosis of HCC in the United States is 65 years. Seventy-four percent of cases occur in men. In patients younger than 40 years of age who present with liver cancer, only a third are HCC; others include fibrolamellar carcinoma, which has a much better prognosis, and metastatic cancer.

In patients with metastatic liver cancer, the primary lesion may not be known. Thus the initial presentation may be due to the metastatic disease to the liver. About half of the patients who die from malignant disease have metastases in the liver at postmortem examination.

Abdominal pain is a common complaint of patients with primary HCC or metastatic liver disease. Some patients have nonspecific complaints, such as anorexia, weight loss, and malaise.

The liver typically is enlarged and nodular and may be tender. Ascites often has developed. A friction rub heard over the liver with respiration indicates involvement of the liver capsule. Rarely, a bruit is heard, reflecting the vascular nature of most HCC and some metastatic tumors. Jaundice usually develops later in the course of both HCC and metastatic liver disease. If jaundice is present initially, it means that preexisting liver disease is present, the tumor involves much of the liver parenchyma, or a large bile duct is obstructed.

Anemia is common in patients with liver cancer. It may be the nonspecific anemia of chronic disease or the macrocytic anemia associated with a chronic liver disorder. Bilirubin is elevated for the same reasons that the patient may be jaundiced (see section I.A.2). Elevation of alkaline phosphatase is common simply because obstruction of even the small biliary radicals causes generation and release of this enzyme. If the source of an elevated alkaline phosphatase level is in question, a 59-nucleotidase elevation will confirm its origin in the liver. Often mild elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) occur.

The serum alpha-fetoprotein concentration is elevated in about half of the patients with hepatoma in the United States; thus, the measurement is useful in helping make the diagnosis. However, some patients with gonadal malignancies and metastatic disease to the liver also have elevated serum alpha-fetoprotein.

include ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), dimethylphenylcarbamylmethyliminiodiacetic acid (HIDA) scan, and sulfur colloid liver scan.

Many physicians proceed immediately to CT in the evaluation of liver tumors after the initial blood chemistry studies have been done. The CT scan has the advantage of not only providing accurate information about the liver but also identifying enlarged lymph nodes and other abnormalities of the abdominal organs. Furthermore, a CT-guided needle biopsy of a liver lesion or other abdominal mass may provide important diagnostic information.